Cystathioninuria, also called cystathionase deficiency, is an
autosomal recessive. It is characterized by an abnormal accumulation of plasma cystathionine leading to excess cystathionine in the urine. Hereditary cystathioninuria is associated with the reduced activity of the enzyme
cystathionine gamma-lyase.
It is considered a biochemical anomaly. This is because it associated with a wide range of diseases and its inconsistency.
Cystathionase catalyzes cystathionine to cysteine and α-ketobutyrate.
Cysteine is an essential amino acid and its conversion from cystathionine occurs in the trans-sulfuration pathway. The availability of cysteine is necessary for the synthesis of an important anti-oxidant, glutathione.
Cystathionase has a co-enzyme, pyridoxal phosphate, which is the active form the vitamin B6. This means that vitamin B6 is essential for the function of cystathionase.
Cystathioninuria can be broken down into two main categories. Primary cystathioninuria is caused by the recessive inherited deficiency of cystathionase enzyme.
Secondary cystathioninuria is described by non-genetic conditions of excess cystathionine. Secondary cystathioninuria includes temporary excess cystathionine of premature infants, severe generalized liver damage, thyrotoxicosis, hepatoblastoma, or neuroblastoma.
Cases of secondary cystathioninuria are not responsive to vitamin B6 administration.
Types
Under primary cystathioninuria, the inherited mutation of CTH gene, there are two forms. There is ''vitamin B6 – unresponsive'' and ''vitamin B6 – responsive'' cystathioninuria.
The vitamin B6 – unresponsive form is thought to be from a lack of the synthesis of cystathionase. This means that the mutation in CTH from this form of cystathioninuria, results in the absence of cystathionase. It could also result from the synthesis of a cystathionase that is so greatly mutated it cannot function at all.
On the other hand, vitamin B6 – responsive form still has synthesis of cystathionase. However, the cystathionase has an altered ability to bind to vitamin B6, its coenzyme.
This changed interaction lowers the efficiency of cystathionase, so it cannot convert cystathionine as well.
Genetics
Cystathioninuria is inherited in an autosomal recessive manner.
[ This means the defective gene responsible for the disorder is located on an ]autosome
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Interestingly, homozygotes and heterozygotes were able to be distinguished in one study through both plasma and urinary levels of cystathionine.single nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in exon 12 was also identified. The presence of various CTH mutations is consistent with the various categories associated with cystathioninuria.
Diagnosis
The main way to diagnosis cystathioninuria is simply through increased urinary excretion of cystathionine. In some cases, a genetic test is employed.
Treatment
The treatment, if any is available, varies depending on the category of cystathioninuria a patient has. The vitamin B6 – responsive form is best treated by an increased consumption of vitamin B6.
References
External links
Amino acid metabolism disorders
Autosomal recessive disorders
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